CD99 antigen (Cluster of differentiation 99) also known as MIC2 or single-chain type-1 glycoprotein is a heavily O-glycosylated transmembrane protein that is encoded by the CD99 gene in humans. CD99 has a key role in several biological processes, including cell adhesion, migration, and apoptosis; differentiation of T cells and thymocytes; diapedesis of lymphocytes to inflamed vascular endothelium; maintenance of cellular morphology; and regulation of intracellular membrane protein trafficking.
CD99 was originally described as a human thymus-leukemia antigen and found to be expressed brightly on cortical thymocytes and T-lineage acute lymphoblastic leukemia (T-ALL), whereas normal peripheral blood lymphocytes appeared to exhibit only low expression levels. It has been reported and used as a marker for detection of minimal residual disease (MRD) in T-ALL. In addition, CD99 is found on the cell surface of Ewing's sarcoma tumors (EWS) and is positive in granulosa cell tumors. Cell surface expression of CD99 is a very consistent feature of EWS, and indeed, CD99 is currently considered to be one of the best diagnostic immunohistochemical markers for this disease. When CD99 expression is knocked down in human Ewing's sarcoma cells, and those cells are grafted onto mice, development of tumors and bone metastasis is reduced.
CD99 expression on acute myeloid leukemia stem cells (AML LSC) compared to normal hematopoietic stem cell (HSC) has been compared and shown to be increased 5.6 fold in AML LSC compared to HSC, suggesting that CD99 can serve as an AMLSC marker in tumor targeting.
The present invention provides anti-CD99 antibodies having low immunogenicity in humans.